title: Chronic alcohol consumption increases the expression of uncoupling protein-2 and -4 in the brain.
abstract: BACKGROUND
  Chronic alcohol consumption leads to oxidative stress in a variety of cells, especially in brain cells because they have a reduced oxidative metabolism of alcohol. Uncoupling proteins (UCPs) are anion channels of the inner mitochondrial membrane, which can decouple internal respiration. "Mild uncoupling" of the mitochondrial respiratory chain leads to a reduced production of free radicals (reactive oxygen species) and a reduction in oxidative cell stress. The extent to which chronic alcohol consumption regulates UCP-2 and -4 in the brain is still unknown.
  
  
  METHODS
  We examined the effects of a 12-week 5% alcohol diet in the brain of male Wistar rats (n = 34). Cerebral gene and protein expression of UCP-2, -4, as well as Bcl-2, and the release of cytochrome c out of the mitochondria were detected by real-time polymerase chain reaction and Western blot analysis. The percentage of degenerated cells was determined by Fluoro-Jade B staining of brain slices.
  
  
  RESULTS
  Brains of rats with a chronic alcohol diet showed an increased gene and protein expression of UCP-2 and -4. The expression of the antiapoptotic protein Bcl-2 in the brain of the alcohol-treated animals was decreased significantly, whereas cytochrome c release from mitochondria was increased. In addition increased neurodegeneration could be demonstrated in the alcohol-treated animals.
  
  
  CONCLUSIONS
  Chronic alcohol consumption leads to a cerebral induction of UCP-2 and -4 with a simultaneous decrease in the antiapoptotic protein Bcl-2, cytochrome c release from mitochondria and increased neurodegeneration. This study reveals a compensatory effect of UCP-2 and -4 in the brain during chronic alcohol consumption.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Graw
authors.forename: Clarissa
authors.initials: C
authors.lastname: von Haefen
authors.forename: Deniz
authors.initials: D
authors.lastname: Poyraz
authors.forename: Nadine
authors.initials: N
authors.lastname: Möbius
authors.forename: Marco
authors.initials: M
authors.lastname: Sifringer
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Spies
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000096:biosynthesis*; D008297:Male; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D000071245:Mitochondrial Uncoupling Proteins; D051381:Rats; D017208:Rats, Wistar; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; C494853:Slc25a27 protein, rat; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000431:Ethanol
keywords: Apoptosis; Chronic Alcohol Consumption; Neurodegeneration; Uncoupling Proteins